title: Pharmacodynamic effects of different aspirin dosing regimens in type 2 diabetes mellitus patients with coronary artery disease.
abstract: BACKGROUND
  Patients with type 2 diabetes mellitus (T2DM) have reduced aspirin-induced pharmacodynamic effects. This may be attributed to increased platelet turnover rates resulting in an increased proportion of non-aspirin-inhibited platelets during the daily dosing interval. The hypothesis of this study was that an increase in the frequency of drug administration [twice daily (bid) versus once daily (od)] may provide more effective platelet inhibition in T2DM patients.
  
  
  RESULTS
  T2DM patients with stable coronary artery disease were prospectively recruited. Patients modified their aspirin regimen on a weekly basis according to the following scheme: 81 mg/od, 81 mg/bid, 162 mg/od, 162 mg/bid, and 325 mg/od. Pharmacodynamic assessments included light-transmittance aggregometry after arachidonic acid, collagen and adenosine diphosphate stimuli; VerifyNow-Aspirin assay; and serum thromboxane B(2) (TXB(2)) levels. Twenty patients were analyzed. All patients were sensitive and compliant to aspirin irrespective of dose, as assessed by arachidonic acid-induced aggregation. When aspirin was administered once daily, there was no significant effect on platelet reactivity by increasing the once-daily dosing using aspirin-sensitive assays (collagen-induced aggregation and VerifyNow-Aspirin). An increase in aspirin dose by means of a second daily administration was associated with a significant reduction in platelet reactivity assessed by collagen-induced aggregation and VerifyNow-Aspirin between 81 mg/od and 81 mg/bid (P<0.05 for both assays) and between 81 mg/od and 162 mg/bid (P<0.05 for both assays). There was no impact of aspirin dosing regimens on adenosine diphosphate-induced aggregation. A dose-dependent effect of aspirin was observed on serum TXB(2) levels (P=0.003).
  
  
  CONCLUSIONS
  Aspirin dosing regimens are associated with different pharmacodynamic effects in platelets from T2DM patients and stable coronary artery disease, with a twice-daily, low-dose aspirin administration resulting in greater platelet inhibition than once-daily administration as assessed by aspirin-sensitive assays and a dose-dependent effect on serum TXB(2) levels. The clinical implications of a modified aspirin regimen tailored to T2DM patients warrant further investigation.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01201785.
authors.affiliation: University of Florida College of Medicine-Jacksonville, Jacksonville, FL 32209, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Capodanno
authors.forename: Aasita
authors.initials: A
authors.lastname: Patel
authors.forename: Kodlipet
authors.initials: K
authors.lastname: Dharmashankar
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ferreiro
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Murali
authors.initials: M
authors.lastname: Kodali
authors.forename: Salvatore D
authors.initials: SD
authors.lastname: Tomasello
authors.forename: Piera
authors.initials: P
authors.lastname: Capranzano
authors.forename: Naveen
authors.initials: N
authors.lastname: Seecheran
authors.forename: Andrew
authors.initials: A
authors.lastname: Darlington
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011446:Prospective Studies; D013929:Thromboxane B2 / Q000097:blood
chemical_list: D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D001241:Aspirin